Chronic Obstructive Pulmonary Disease
Chronic Obstructive Pulmonary Disease (“COPD”) affects middle aged and elderly people, and is one of the leading causes of morbidity and mortality worldwide affecting as many as 14 million people in the United States. The World Health Organization predicts that by 2020 COPD will become the 5th most prevalent disease, and the 3rd most common cause of death (see P. J. Barnes, New Engl. Journ. Med. 343:269-279 (2000)). COPD is associated with major healthcare costs, largely due to expensive treatments such as long-term oxygen therapy and hospital admissions, as well as indirect costs including loss of working capacity. Recent epidemiological data suggests that the prevalence of the disease is underestimated.
COPD is characterized by a reduction in expiratory flow and slow forced emptying of the lungs which does not change markedly over several months
Cigarette smoking (especially, long term cigarette smoking) is believed to be the leading cause of COPD (statistically, a smoker is 10 times more likely than a non-smoker to develop and die of COPD). Smoking cessation is the only measure that will slow the progression of COPD. Airflow obstruction in COPD is usually progressive in patients who continue to smoke eventually leading to disability and shortened survival time. Smoking cessation has been shown to slow the rate of decline to that of a non-smoker but the damage caused by smoking is irreversible.
Other etiological factors (e.g., airway hyper responsiveness or hypersensitivi air pollution (e.g., sulfur dioxide and possibly second hand smoke), occupational chemicals (e.g., cadmium) and generally allergy) have been identified in the literature but are believed to account for only a minority of COPD cases. Other risk factors include: heredity, second-hand smoke, exposure to air pollution at work and in the environment, and a history of childhood respiratory infections.
COPD often entails: chronic coughing, frequent chest tightness, shortness of breath, an increased effort to breathe, increased mucus production, and frequent clearing of the throat. COPD is characterized by airflow obstruction caused by chronic bronchitis, emphysema, or both. Airway obstruction is incompletely reversible but some COPD patients do show some improvement in airway obstruction with treatment. Airway obstruction due to chronic and excessive secretion of abnormal airway mucus, inflammation, bronchospasm, and infection are believed to cause chronic bronchitis leading to chronic cough, mucus production or both. In emphysema instead, the elastin in the terminal bronchioles is destroyed leading to the collapse of the airway walls and inability to exhale. Emphysema is characterized by the destruction of the alveoli and the abnormal permanent enlargement of the air spaces distal to the terminal bronchioles, accompanied by destruction of their walls without apparent fibrosis (for a more detailed description see, Harrison's Principles of Internal Medicine, 12th Edition, Wilson, et al., eds., McGraw-Hill, Inc.).
Asthma by contrast, often has an onset in infancy, childhood or adolescence, though sometimes it may become manifest in the adult. It is often caused by exposure to an allergen, and is mediated by an immune system involving IgE. Patients typically present with acute shortness of breath, wheeze, cough, and congestion. Bronchial spasms of the airway are typically reversible with treatment, although in some cases there may be chronic bronchial obstruction due to thickening (remodeling) of the bronchial wall (for a more detailed description see, Harrison's Principles of Internal Medicine, 12th Edition, Wilson, et al., eds., McGraw-Hill, Inc.).
COPD: Therapies Available
Presently available treatments are merely ameliorative. They include avoidance of irritants such as tobacco smoke and breathing supplemental oxygen. In advanced cases of COPD, lung reduction surgery is sometimes performed, but it is not clear that it helps. There is very little currently available to arrest its progression and otherwise prevent its exacerbations, preserve lung function, and otherwise improve the quality of life of COPD patients. The arsenal of medications available to practitioners treating COPD patients have traditionally include: fast-acting, β2-agonists, anticholinergic bronchodilators, long-acting bronchodilators, antibiotics, and expectorants. Amongst the currently available treatments for COPD, short term benefits, but not long term effects, were found on its progression, from administration of anti-cholinergic drugs, adrenergic agonists, and oral steroids. Oral steroids are only recommended for acute exacerbations with long term use contributing to excess mortality and morbidity.
Short and long acting inhaled, adrenergic agonists are used to achieve bronchodilation and provide some symptomatic relief in COPD patients. This class of drugs has been shown to have no maintenance effect on the progression of the disease. Short acting adrenergic agonists improve symptoms in subjects with COPD, such as increasing exercise capacity and produce some degree of bronchodilation, and even an increase in lung function in some severe cases. The maximum effectiveness of the newer long acting inhaled, adrenergic agonists was found to be comparable to that of short acting, adrenergic agonists. Salmeterol was found to improve symptoms and quality of life, although only producing modest or no change in lung function. Notably, β-agonists can produce cardiovascular effects, such as altered pulse rate, blood pressure; and electrocardiogram results. Treatment of asthmatic and COPD patients with the bronchodilators ipratropium bromide or fenoterol was not superior to treatment on an as-needed basis, therefore indicating that they are not suitable for maintenance treatment. The combination of a β adrenergic agonist with an anti-cholinergic drug provides little additional bronchodilation compared with either drug alone. The addition of ipratropium to a standard dose of inhaled, β adrenergic agonists for about 90 days, however, produces some improvement in stable COPD patients over either drug alone. Overall, the occurrence of adverse effects with β adrenergic agonists, such as tremor and dysrhythmias, is more frequent than with anti-cholinergics. Thus, neither anti-cholinergic drugs nor, β-adrenergic agonists have an effect on all people with COPD; nor do the two agents combined.
Antibiotics are also often given at the first sign of a respiratory infection to prevent further damage and infection in diseased lungs. Expectorants help loosen and expel mucus secretions to from the airways, and may help make breathing easier. In addition, other medications may be prescribed to manage conditions associated with COPD. These may include: diuretics (which are given as therapy to avoid excess water retention associated with right-heart failure), digitalis (which strengthens the force of the heartbeat), and cough suppressants. This latter list of medications help alleviate symptoms associated with COPD but do not treat COPD.
Thus, there is very little currently available to alleviate symptoms of COPD, prevent exacerbations, preserve optimal lung function, and improve daily living activities and quality of life.